We are investigating the natural history of the receptors for immunoglobulin E (IgE) and immunoglobulin on mast cells and basophils. We aim to study the mode of function and turnover of the free and ligand bound receptors and the fate of the cell bound IgE before, during and after exocytosis of mediators of the allergic response which is initiated by aggregation of surface bound IgE. We found that monomeric IgE molecules remain resident on the cell surface for over 250 hrs and endocytosis is only affected by crosslinking of surface bound molecules. The minimal size aggregate required to signal internalization was dimeric. Interestingly, dimers provide only a poor signal for histamine release from RBL cells. Internalized IgE is later released, the receptor internalizes with the ligand and does not appear to be reusable. Aggregates of IgG are also endocytosed. Empty receptors for IgE and monomeric IgE cointernalize with crosslinked IgE but not with crosslinked surface bound IgG. Unlike the process of mediator release, internalization of aggregated IgE by RBL and normal mast cells is independent of calcium and proceeds at a different rate. Endocytosis could account, in part, for the phenomenon of desensitization. It is hoped that further clarification of these aspects of mast cell and basophil function would lead to better understanding of the allergic response.